Abstract

Rapid determination of bacterial antibiotic susceptibility is important for proper treatment of infections. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has recently published guidelines for rapid antimicrobial susceptibility testing (RAST) performed directly from positive blood culture vials. These guidelines, however, were only published for a limited number of common pathogenic bacteria. In this study, we evaluated the applicability of these guidelines to three Tier 1 bioterror agents (Bacillus anthracis, Yersinia pestis and Francisella tularensis) that require prompt antibiotic treatment to mitigate morbidity and mortality. We used spiked-in human blood incubated in a BACTEC™ FX40 system to determine the proper conditions for RAST using disc-diffusion and Etest assays. We found that reliable disc-diffusion inhibition diameters and Etest MIC values could be obtained in remarkably short times. Compared to the EUCAST-recommended disc-diffusion assays that will require adjusted clinical breakpoint tables, Etest-based RAST was advantageous, as the obtained MIC values were similar to the standard MIC values, enabling the use of established category breakpoint tables. Our results demonstrate the promising applicability of the EUCAST RAST for B. anthracis-, Y. pestis- or F. tularensis-positive blood cultures, which can lead to shorter diagnostics and prompt antibiotic treatment of these dangerous pathogens.

Highlights

  • B. anthracis, Y. pestis and F. tularensis are three pathogens that are categorized by theU.S Centers for Disease Control and Prevention (CDC) as Tier 1 biological select agents [1].Without proper treatment, high rates of mortality are observed within a short period following infection [2,3,4,5]

  • We sought to evaluate whether these shortcuts could be applied to B. anthracis, Y. pestis and F. tularensis, three Tier 1 select agents on the CDC list for which rapid antimicrobial susceptibility testing (RAST) can be beneficial

  • As was observed for the standard culture, for most antibiotics, the diameters at the shortened reading times were different from those of the longer reading times. These results suggest that RAST performed directly from Blood cultures (BCs) is feasible for B. anthracis, specific interpretation breakpoint tables should be established for shorter reading times

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Summary

Introduction

B. anthracis, Y. pestis and F. tularensis are three pathogens that are categorized by the. High rates of mortality are observed within a short period following infection [2,3,4,5]. These characteristics led to the recognition of these pathogens as potential biological threat agents. The disease caused by B. anthracis, can appear in three major forms: cutaneous, gastrointestinal and inhalational. Y. pestis is the etiological agent of plague, a severe and fatal disease. This disease has several major forms, bubonic, pneumonic and septicemic, Microorganisms 2021, 9, 1055.

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